A basic mystery in developmental biology is how genes function to organize the growth and patterning of the developing embryo. In the fruit fly, Drosophila, genes have been identified which appear to function as developmental switches. Cells which would normally follow one developmental pathway can be switched to another by mutations in the regulatory genes. A cluster of such genes, the Antennapedia Complex (ANT-C), has been extensively studied using genetic and molecular approaches. The proposed research is directed at understanding, at the molecular level, how the genes function to control development. Within the ANT-C are several homoeotic genes in which mutations cause altered cell fates. Mutations in the Antp gene, for example, can cause legs to develop where antennae would normally be. The ANT-C also includes the segmentation gene ftz, in which mutations cause embryos to develop with half the normal number of body segments. The project is focused on Antp, ftz, and another homoeotic gene, Ser. The specific aims are: 1) To further characterize the structure of the three genes in their wild type and mutant forms, especially to understand how the genes are expressed at the right positions and times in the embryo. 2) To determine the molecular functions of the protein products of the genes, in order to understand the basis of regulatory properties of the genes. and 3) To study the interactions between the ANT-C genes and other genes involved in controlling development. Each of the three genes contains a "homoeobox", a 180 bp DNA sequence encoding a highly conserved 60 amino acid protein domain, which is hypothesized to be involved in sequence-specific DNA binding. Since homoeoboxes are present in higher vertebrates, including humans, studies of the molecular functions of the ANT-C genes may provide information relevant to human early development.